Azo intermediates



i or the tautomeneformfin whih the" `Patentecl"Jan."2, 1945 A UNITED STATES PMEMEA o r to E. I. du Pont de `Nemenifs-15in` Company, Wilmington, Del., a corporation.olllelaware No Drawing. Apiiiiationmayci raiz;y r -1 v- Serial No. Mlgflwy 1` "111: claims..`

`(li-cin as l i (1J-Fon ySome l of the hydrazoes' may beI isolated as group is represented intermediate products `having the general, fori mula-:f i .l M .i .t

" -HNn= IJ;oH2C-0R NOM.

`Irtlieser `formul'aeX.'ishoneoinmore` 4of the' com` `mon`- substituents which arefound ion'A aryliinu-` clelyj such as alkyl; sulfonic acid; halogen.` car`- i boxylic acid-hydroxy; nitro, andf i N`CH i Y is from the group alkyl, carboxy, orcarboxy alkyl; and.` Rfiis; alkyl. Exemplary@ of? such` i are ther nitro-arylehytlrazonesy of@` oxalaceticacid" OneIk of `tlfievuseiul aproductsswhich canine-pros ducedl'byirmy processes; the punitivophenylfhy-V drazoneiofoxalaceticeaciddmonoaethyl ester, vhas been madeH before by1 other.' means,y `butwtheufor` mer" processes' are i diflicult 1 of; manipulatiom and It isi, an` objectofsfthis invention to Vmakewhys drazones' and pyrazol'onesfv byi processes .'vwhicliv are technically-eminent and: economi@anwV sangra t Theobj ects of( the invention are( acconlplished` byfl a. process,y 1 or processes; i in Which'f a1 selected nitroarylam'ine is tdiazotizedl tot producers diano?I In this:- specification I will use the` (ci. ato-ann.'

. nium salt; fthe-2 diazoniuml salt( is @comrertedA to alkali :salti of. as nitroaryl'hhyclrazineasulfonic` La'cid: by'. reaction with. aamixtu're'; on: alkali@suliit'e` and:l alkalii'bis'ult'e;these sulfonioffacidffsaltsrareethen;

5 inl `dis"tinotionl-ifrom fpriora processes-1wiiioliirequire their: sulostantially` completen?.hydrolysis beforec i condensation;` condensed( directlyff with.. a ketocarboxylicl acidester. in 1 strong niineralf'acid Ine-.- diurni tol" produce*.eithery a hydraZone-f'or: the i cor responding;` pyrazolbnes; dependingL on whethe-n on'notllthehydrazone rings close tothe pyrazolone in: .thea acid mediuzrr` offtfhel bath".l orf require iur-'-` ther treatment to close theiringsa In @cases-where ringrolosure does n'ot'takeV placein( acidi medium,`

thef hydrazonef. may` loe'M ring-llclo'sed inf.v alkaline being insmubie-:iimacidvisiprecipitates'fbwalciuinl i cation andzisolatedrby flltrationfl.. i

Thee primari ."aryl'arninesr usedf to produce tle particular.1 type `off' compounds for-m the preferred products sofxmyrprocessiare .represented `byltheyviorm'ula:` i f i i i 1Tl0lial"z.

4 inwhiqh:sigasdefined-hereinabove; t

Theketoarboxylicacid estersl used in the process offtheinventionare off'the type:v

are:A called?` beta-ketocanboxylc.; acidi estersrherein." `Alli the beta-lieto esters( mayf beL used directlyfy asf suoli; but* i inv thef case oi*` frea'ctionsf i'nvolvingf beta-kater estersw inw-rwliinl'l@` thefsubstitu desirable tof produce a-.hydrazone zona. pyrazol'orre which the substituentfx` isf a freek Vcarboxylic acid* groupfinsteadt of:r` ani'ester group; Innsuch cases; iti,isadvantageousijto; convertrf tliergroup medium. Biieily` andigenerally.I descr-Hoed;V in

ann the1 eni-I isA atcarboxylic estenigroupi-it fisfrequently or potassium bisulfite andammonium, sodium,

fore the compound is reacted with the hydrazine sulfonate. This is accomplished by reacting the diester with sodium hydroxide in solution. The

hydrolysis may, less deslrably, be carried out after the formation of the keto-pyrazoline.

lAlthough processes vof diazotization are Wellknown, a satisfactory one for use in my process is as follows: A nitro-arylamine of the type describedl is diazotized in an excess of mineral acid with sodium nitrite solution. Hydrochloric acid is the preferred mineral acid 'and is used in thev amount of about 2.5 Amols 'of hydrochloric acid per mol of the amine. The sodium nitrite is preferably added as a solution of 25 to 40% by weight in an amount which is slightly in excess of one mol of nitrite per mol of amine. The temperature is preferably kept 4below 10 C.

The diazonium salt solution'whichfhas been so prepared is neutralized with a mild base so that itlshows faint acidity on Congo red paper. Sodium bicarbonate is an excellent neutralizer but is only representative of -other mild bases such as alkali earbonates, alkali bicarbonates, oxides, carbonates ofmagnesium and calcium and weak organic acid salts of these metals, such as sodium acetate. The neutralization is preferably carried out in they cold, a satisfactory temperaturebeing under C. but higher temperatures may be used without disadvantage in connection with yparticular salts. i

The neutralized diazonium salt solution is mixed with a solution of ammonium, sodium,

or potassium sulte. 'Ihis mixture may be made by the use of bisulfite and alkali or by the use of sulrlte and acid, or bymixing sulte and bisulte together. The reaction between theneu.- tralized salt and the mixture of sulte and-bisul- 40 te preferably takes place in the cold, tempera.-V tures from 5-15 C. being satisfactory, but tem-- peratures up to 25 C. or beyond are not deleterious with certain compounds. The bijsulfite and fifi' the sulflte should each be in excess of one mol `per mol of amine, and the excess should be sufficient to keep the pH of the solution acid` to litmus ,and neutral to Congo'redpaper during the addition of the diazonium salt solution'. The reaction should be carried out .With good agitation and the mixing of the two'solutions should not take longer than ittakes the solution to' turn acid to Congo red spontaneously. This time will vary with the temperature, with the concenl tration of sulte and bisulte and with the particular diazonium salt.y

It is preferable at this point to add some strong mineral acid, such as sulfuric acid, to the solution of the dialkali-disulfonate in orderto conver-t or partially convert it to the monosulfonate and, in cases where alkaline hydrolysis of `the beta-keto-dicarboxylic esters has been made, t neutralize the alkali salts of these esters.

To the mixture of hydrazine sulfonic acids formed by the vforegoing process is added the lieto-carboxylic acid ester orits alkali complex and strong mineralacids, such as sulfuric or hydrochloric acid. The keto-carboxylic acid should be present in an excess of about 10-20%v per mol of hydrazine sulfonate.: Lesser amounts decrease the yield and quality but greater amounts may be used -without inefficiency. The amounts ofmineral acid which are addedand the temperatures usedvarywwidely with the individual ketone and the individual hydrazine sulfonate. 'I

This process is represented bythe following reactions:

1. Diazotization:

(para-nitro-phenyl-diazonium chloride) Para-nitro-phenyl-diazonium ch1oride+NaHSOa+Na2SOg SOaNa (p-nitro-phenyl-hydrazine-disodjum-disulfonate) Add mineral acid to the hydrazine disulfonate and combine AN=cc0011 The following examples illustrate but do not limit the invention.

Example I ll C-CHa 138 parts of p-nitro-aniline was thoroughly mixed rwith 200 parts of Water until a smooth paste was obtained. To this paste was added 300 parts of 31% hydrochloric acidand 300, parts Lof, ice. The mixture was agitated in an icezbath as 230 parts of 30%',sodum nitrite was added over a period of about two minutes during which time the temperature rose from 5 C..to 10 C. Agitation was continued for about an hour at 5 to'lO" C'. Y l i 'While the diazonium chloride solution `was being agitated the following mixture was prepared: parts of 30% sodium hydroxide was added to 650 parts of a 38% solution of sodiumbisulflte. This suspension of sodium sulflte and` ybisulte was cooled to 15 C. with external cooling..l The diazonium chloride solution was carefully.k neu-f' tralized with finely ground sodium bicarbonate in small portions, until the solution; gave. only faintI brownstreaks on Congo red paper.- i

This neutralized solutionv was added tothe well agitated mixture of sodium sulte and bisulfte over a 4period of about twenty minutes, the perature being maintained atlo to 20 `C`., and the pH checked to make sure thesolutionfwas at all times neutral to Congored 'andacidj-to the blue litmus papers. The resulting golden presence of mineral acids, and it could not be anticipated by reference to the literature that re.. action of the keto ester and the hydrazine sulfonic acid would take place at all, let alone take place more rapidly than the decomposition of the ketocarboxylicfacid ester. According to the methods described in the literature, the hydrazine sulfonic acids are hydrolyzed to the hydrazine before the condensation is made With keto esters.

As many apparently Widely different embodiments of this invention may be made Without departing from the spirit and scope thereof, it is to be understood that I do not limit myself to the specific embodiments thereof except as defined in the appended claims.

I claim: l Y

1. vThe process of making a nitro-phenyl-pyrazclone-carboxylicv acid which comprises reacting para-nitro-benzene diazonium chloride with a sulte and a bisulte, reacting the diethylester of oXal-acetic acid with NaOl-I in solution at 20-25 C. to produce the disodium salt of oxal-ethyl acetate, reacting the said disodium salt with the product of the sulte-bisulte reaction in the presence of sulfuric acid in sufficient' amount to cause the formation of the para-nitro-phenylhydrazone of oxalacetic acid at a temperature about 90 C. with agitation, filtering off and dissolving the product in alkali solution and precipitating the pyrazolone with acid.

2. The process of making a nitro-phenyl-pyrazclone-carboxylic acid which comprises reacting a nitro-phenyl-diazonium` chloride With a` sulte and a bisulte, reacting the product of that reaction with the sodium salt of an ethyl ester of oxalacetic acid in the presence of enough sulfuric acid to form the hydrazone of oxalacetic acid and at temperature elevated to less than 100 C. with agitation, closing the ring of the compound by the action of alkali, and isolating the pyrazolone.

3. The process of making a nitro-phenyl-pyrazclone-carboxylic acid which comprises reacting a nitro-phenyl-diazonium chloride With a sulte and a bisulte, reacting the product of that reaction with the sodium salt of an ethyl ester of oxal-acetic acid in the presence of enough acid to form the hydrazone of oxalacetic acid, and at temperature elevated to less than 100 C. with agitation, and isolating the pyrazolone.

4. The processfor the manufacture of pnitro phenyl-pyrazolone carboxylic acid represented by the formula: f

c-CH .which comprises adding a solution of disodium nitro-phenyl diazonium salt of a mineral acid) withfa solution of dis'odium -monoethyloxalacetate, and adding sulfuric acid to the mixturel in f sufficient amount to cause the formation of the.`

nitro-phenyl-hydrazone o-f monoethyl oxalacetic acid y y I, -NH-N=o`om l-oo2nr I 02H O Y NO2 at a temperature under 100 C., filtering orf the hydrazone and treating it with alkali to form pyrazolone,

Il C-CH2 prises mixing an -acidied nitro-phenyl-hydrazine sulfonic acid solution (prepared by reducing with a mixture of sulflte and bisulfite a solution of nitro-phenyl diazonium 'salt of a mineral acid) with a solution of disodium monoethyl oxalacetate, and adding sulfuric acid to the mixture in sufficient amount to cause the formation of the pyrazolone, represented by the formula shown in claim 5, at a temperature under 100 C.

7. The process for the manufacture of nitro" phenyl-pyrazolone carboxylic acid represented by the formula shown in claim 5, which comprises adding to an acidied mixture of nitro-phenylhydrazine mono anddisulfonic acid, a solution of disodium mono-alkyl-oxalacetate, adding sufficient mineral acid to the mixture to cause the formation of the nitro-phenyl-hydrazone of mono-alkyl-oxalacetic acid,

at a temperature under C., filtering off the hydrazone and treating it with alkali to form the H C-CHz 'which comprises reacting ethyl-aceto-acetate with nitro-phenyl hydrazine sulfonic acid in the presence of sufficient mineral acid to cause the formation of the pyrazolone at a temperatur under 100 C. f

l 9. The process for the manufacture of a nitrophenyl-methyl-pyrazolone represented by .the formula: y

which comprises reacting ethyl-aceto-acetate with a mixture of nitro-'phenyl-hydrazine mono and disulfonic acids in the presence of sufficient mineral acid to cause the formation of the pyrazolone at atemperature under 100 C.

, 10. The process for the manufacture of p-nitrof the phenyl-methyl-pyrazolone` represented by the formula @NQ-M N= -CHz which comprises reacting `ethyl-aceto-acetate Il C-CHI with p-nitro-phenyl-hydrazine sulfonc acid` in u the presence of sufficient mineral acid to cause the formation of the pyrazolone at a temperature under 100 C. l u u' 11. The process for the manufacture of pnitrophenyl-methyl-pyrazolone represented Y by the formula.: t

and disulfonic acids in the presence of sufficient mineral acid to cause the formationof the pyrazo i lone at a temperature under 100 C.

i CHARLES J. HARRINGTON. 

